Neurologic complications and related diseases, including HIV-1 associated neurocognitive disorders or HAND, remain one of the most devastating clinical manifestations of HIV-1 infection even after treatment with antiretroviral therapy. Accordingly, it is now well recognized that a novel strategy is needed to eradicate AIDS and its associated co-morbidities as current antiretroviral therapies have failed to eliminate HIV-1 from the infected host. Here, we seek support to continue operation of a highly needed Comprehensive NeuroAIDS Core Center (CNAC) that was established in 2011 at the Temple University School of Medicine in partnership with Drexel University College of Medicine in Philadelphia to provide infrastructure for performing innovative research in the neuroscience of HIV-1/AIDS. The central theme of CNAC, in the second round of funding, will be to foster an environment for performing translational research in neuroAIDS by offering expertise and service in molecular and cellular biology as well as the genetics and virology of HIV-1 infection of the CNS using in vitro, in vivo, and ex vivo systems provided by the various cores. It is our goal that CNAC promotes research toward understanding mechanisms responsible for HAND and provide new paths for the eradication of infected cells and viruses and the treatment of AIDS/CNS disease. Accordingly, more emphasis will be on cell- and viral-based methodologies and the assessment of the impact of HIV-1 on cell function pertaining to CNS diseases. To accomplish our goal, the CNAC will provide expertise in neural cell cultures, viral reagents, microelectrode array, gene editing strategies, and high end proteomics/metabolomics through its Basic Science Core I (BSC I). Basic Science Core II (BSC II) will provide expertise and facilities in the employment of animal models for studying HIV-1 brain interaction and behavioral testing/training and histological training and related services. The Clinical and Translational Research Support Core (CTRSC) of the CNAC, with greater than 2,000 patients participating in two well-characterized/controlled cohorts at Temple University Hospital (North Philadelphia) and Drexel's Hahnemann Hospital (Center City Philadelphia) will support development and maintenance of cohesive IRB protocols, offer expertise in cognitive performance and neuropsychology, virology/immunology and immunoactivation, and viral genetics/genomics and bioinformatics. Through the Developmental Core, the CNAC will offer a unique opportunity for training and mentoring of junior investigators and clinical investigators, and attract and develop physicians/scientists in the field of neuroAIDS. The CNAC will provide infrastructure by i) providing start-up funds through its Developmental Core, ii) offering intellectual support and technical services through its state-of-the-art basic science cores and iii) access to an expansive well-operating clinical core, for conducting innovative research toward the development of intelligent, effective, and safe genetic and cellular/immunologic strategies toward a cure of AIDS. Further, the funding through CNAC will create an environment for the development of collaborative research in neuroAIDS at Temple, Drexel and other medical institutions in the greater Philadelphia area, and extend its collaboration with other AIDS research centers in Philadelphia and the nation.